Previous studies have shown that adenylate cyclase activity of fibroblasts in culture is altered following viral transformation and during various stages of cell growth. Thus, it is of interest to elucidate how the activity of adenylate cyclase might be altered and regulated by both intra- and extra-cellular agents and events. We have found that cyclase activity in the AD6 mutant of Balb 3T3 cells is not changed and retains its hormonal responsiveness even though cholera toxin activation is decreased. Since AD6 cells are defective in glycolipid (ganglioside) and glycoprotein synthesis, these results suggest that changes in membrane structure other than modification of the carbohydrate moieties are responsible for the loss of growth control and the altered properties of adenylate cyclase noted with transformed cells. Serum factor(s) may play a significant role in the regulation of adenylate cyclase. We have isolated a factor from calf serum which selectively inhibits the GTP functions of this complex enzyme system. In other studies we have found that the cyclase activity of isolated membrane preparations is markedly enhanced by low concentrations of trypsin or certain other proteolytic enzymes. The mode of action and physiological significance of these regulatory effectors remains to be established. BIBLIOGRAPHIC REFERENCES: Anderson, W.B., and Jaworski, C.J.: Modulation of adenylate cyclase activity of fibroblasts by free fatty acids and phospholipids. Arch. Biochem. Biophys., in press, 1977. Anderson, W.B., and Jaworski, C.J.: Adenylate cyclase activity of normal and transformed fibroblasts in culture. Proceedings of the Third Dicennial Review Conference, in press, 1977.